The function of the Microarray Core will be to provide full support for Diabetes Endocrinology Research Center (DERC) projects undertaking gene expression studies by microarray analysis and will encompass a range of support mechanisms, including: 1) technical services, 2) training, 3) resources and equipment, and 4) consultation and expertise. The structure of the Core will be organized around two principal components, array screening and data analysis. Screening services will include preparation of total RNA and/or mRNA, probe labeling and purification, array hybridization and washing and scanning of hybridized arrays. Spotted glass slides and Affymetrix chips will be obtained from the W. M. Keck Microarray Resource here at Yale. Data analysis services will include numerical quantitation of fluorescence intensities, signal normalization, statistical testing and data mining. Validation of identified changes in gene expression will be carried out by subsequent quantitation using real-time PCR and/or RNase protection. We will optimize the elements of microarray analysis that have been determined to be critical to obtaining reliable data and valid conclusions. These are: 1) the choice and quality of array template, both the form (cDNA or oligonucleotide) and the substrate (glass slide or chip), 2) the quality of input RNA for probe preparation, 3) the rigor and power of statistical testing, both in terms of experimental design and assessing data reliability, 4) the database resources for data entry, access, annotation and linkage, and 5) the tools for data mining and functional informatics.